Inhibitors of human phosphatidylinositol 3-kinase delta

Abstract

Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3Kδ) activity, and methods of treating diseases, such as disorders of immunity and inflammation, in which PI3Kδ plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3Kδ, while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3Kδ activity, including compounds that selectively inhibit PI3Kδ activity. Methods of using PI3Kδ inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3Kδ inhibitory compounds to inhibit PI3Kδ-mediated processes in vitro and in vivo.

What is claimed is: 
     
       1. A compound of formula IV 
       
         
           
           
               
               
           
         
         wherein Y is null; 
         R 10  is selected from the group consisting of H, halo, OH, OCH 3 , CH 3 , and CF 3 ; 
         R 11  is selected from the group consisting of H, OCH 3 , and halo; 
         R 12  is selected from the group consisting of phenyl, halophenyl, and alkylphenyl; 
         R d , independently, is selected from the group consisting of NH 2 , NH(C 1-3 alkyl), N(C 1-3 alkyl) 2 , and C 1-3 alkyl; and 
         q is 1 or 2; 
         or a pharmaceutically acceptable salt thereof; 
         provided that: 
         (a) at least one of R 10  and R 11  is different from 6-halo or 6,7-dimethoxy groups; and 
         (b) R 12  is different from 4-chlorophenyl. 
       
     
     
       2. The compound of  claim 1 , wherein R 12  is alkylphenyl, or a pharmaceutically acceptable salt thereof. 
     
     
       3. The compound of  claim 2 , wherein R 10  is CH 3  and R 11  is H, or a pharmaceutically acceptable salt thereof. 
     
     
       4. The compound of  claim 3 , wherein R d  is NH 2 , or a pharmaceutically acceptable salt thereof. 
     
     
       5. The compound of  claim 1 , wherein the compound is 2-(6-aminopurin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one, or a pharmaceutically acceptable salt thereof. 
     
     
       6. A pharmaceutical composition comprising an effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient. 
     
     
       7. A pharmaceutical composition comprising an effective amount of a compound of 2-(6-aminopurin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient.